Ion Transport by Pulmonary Epithelia

Figure 2

Schematic drawing of ciliated airway epithelial cells with Na⁺, Cl⁻, and K⁺ channels and transporters. On the apical side, the airway epithelium is covered by the airway surface liquid that consists of the periciliary liquid (PCL) surrounding the cilia and the mucus layer covering the cilia. The mucus layer with its trapped particles is transported orally by ciliary beat of the ciliated epithelial cells. The composition of the PCL is regulated by ion transport processes, mainly apical Na⁺ reabsorption and Cl⁻ secretion, which H₂O follows passively along the osmotic gradient. Due to transparency reasons, the Na⁺, Cl⁻, and K⁺ channels and transporters have been depicted in different cells (left: Na⁺ transport, middle: Cl⁻ channels, right: K⁺ channels), although most of them are usually found in the same cell. The left cell depicts transepithelial Na⁺ reabsorption mediated by concerted activity of apical epithelial Na⁺ channels (ENaC) and the basolateral Na⁺/K⁺ ATPase. Apical cyclic nucleotide-gated cation channels (CNG) might also contribute to Na⁺ reabsorption. Additionally a Na⁺/H⁺ exchanger (NHE) has been identified in airway epithelial cells for regulation of intracellular pH. In addition to Na⁺ reabsorption airway, epithelia display a prominent apical Cl⁻ secretion that is mainly mediated by the cystic fibrosis transmembrane conductance regulator (CFTR) in humans and to a lesser extent by Ca²⁺-dependent Cl⁻ channels (CaCC) such as the TMEM channels (middle cell). This secretion is kept up by the basolateral Na⁺/K⁺/2Cl⁻ cotransporter and the HCO₃⁻/Cl⁻ exchanger (AE). Additionally three basolateral Cl⁻ channel types have been identified: a basolateral outward rectifying channel (BORC), a basolateral inward rectifying channel (BIRC), and a basolateral CFTR-like channel (BCFTR). These channels have been suggested to be involved in modulation of apical Cl⁻ secretion. The right cell depicts the K⁺ channels so far identified in airway epithelium that are supposed to modulate apical Cl⁻ secretion. In the basolateral membrane, several voltage-dependent K⁺ channels have been identified (Kv7.1–Kv7.5). Ca²⁺-dependent K⁺ channels have been characterized in the apical and the basolateral membrane (SK4, BK_Ca, K_Ca3.1).